The overall goal of the research proposed is to examine negative regulation of the antibody response in the context of nonspecific, antigen-induced, suppression (antigenic competition) and T cell-mediated suppression to determine if these models share a common mechanism at the cellular level. The available evidence strongly supports the involvement of a soluble suppressive substance, probably produced by T lymphocytes in response to antigen. The suppressive mechanisms involved in these phenomena will be studied, in parallel, in well-characterized cell transfer, cell impermeable diffusion chamber, and in vitro systems. The target of suppression will be identified in each model. Finally, the soluble suppressors will be isolated and characterized, and the mechanism of action confirmed with regard to the target, using the purified substances.